Use of recombinant viruses to deliver cytokines influencing the course of experimental bacterial infection

Abstract

The feasibility of using viral constructs expressing cytokine genes to influence the course of bacterial infection was tested in mice. The mice were first infected with vaccinia or fowlpox viruses expressing the cytokine of interest, then challenged with the facultative intracellular bacterial pathogen Listeria monocytogenes. The course of infection was assessed by subsequent bacterial counts. Expression of IFN-gamma or TNF was protective. Vaccinia virus was more efficient at delivering IFN-gamma-mediated protection than was fowlpox virus, which is unable to proliferate in mammalian cells. The effect of vaccinia-IFN-gamma was more apparent in the liver, where vaccinia proliferates to high titres (> 109), than in the spleen, where only 103 vaccinia were isolated. Vaccinia virus expressing IL-4 exacerbated infection. Interleukin-4 exacerbation was T cell independent and was reflected in the failure of macrophage activation, possibly due to suppression of NK cells, which are a source of IFN-gamma early in infection. The clear indication of protection by some cytokines in this prophylactic model appears to justify further study of the therapeutic effects of cytokine-expressing viruses in chronic bacterial infections, especially where a cytokine defect is suspected.